Human vulnerability represents an open field of study that allows us, through the use of indicators, to measure a territory’s weakness and potential for dealing with negative climate impacts. This kind of assessment is important within the scope of Sustainable Development Goals (SDGs), especially as a tool that is able to direct the strategies and planning in countries in the context of regional climate change (SDG 13.2). The aim of this work is to demonstrate the application of a method that uses a software created for the Brazilian context (SISVUCLIMA) to evaluate human vulnerability to climate change in the state of Maranhão, Brazil. Via an assessment of socioeconomics, demographics, climate, epidemiological, and environmental aspects compiled to develop a municipal vulnerability index, it was clear that the central and western mesoregions of Maranhão are more fragile regarding exposure, sensitivity, and adaptative capacities. These locations may be the most affected by rising temperatures and reduced rainfall that is projected for the next 20 years in the region. It is believed that the results obtained in this study may contribute indirectly to the adoption of effective actions directed at SDG 13 and other SDGs in the country. By considering the socio-ecological and health determinants that define the vulnerability profile of the municipalities of Maranhão, it will be possible to suggest specific actions to reduce the fragility of the local population to climate impacts. Through a spatial and multi-dimensional view of the problem, the proposed indicators can act as an effective instrument for overall environmental management from a sustainable perspective.